Many generally safe drugs result in severe acute liver injury (drug-induced liver injury, or DILI) in a small percentage of patients. This study seeks to increase our understanding of the genetic risk factors for these events by whole-genome sequencing of 30 individuals experiencing DILI due to the antibiotic combination amoxicillin/clavulanate, discovering novel rare genetic variants, and testing these for association with injury status in a large cohort of DILI cases and controls. This has the potential to identify predictive genetic markers for identification of patients at risk for DILI and, thus, greatly improve the safety of the associated drugs and inform future drug development. PUBLIC HEALTH RELEVANCE: The proposed project seeks to improve our understanding of the genetic factors that contribute to drug-induced liver injury, so as to avoid this severe adverse reaction in patients at risk, and to inform future drug development